: The nucleus accumbens is widely implicated in appetitive behaviors, including intake of food and drugs of abuse. It is also known to be critical to certain forms of learning. Further, distinct subregions of the nucleus accumbens (NAc) seem to regulate specific appetitive or defensive behaviors, including feeding behavior. The predominant type of neuron in the nucleus accumbens is the GABAergic medium spiny neuron. GABAergic neurotransmission in this region is thought to regulate feeding behavior. We propose to compromise GABA function genetically by creating a conditional GAD67 knockout mouse in which we can eliminate GAD67 in a neuroanatoinically exact manner within the nucleus accumbens. We hypothesize that compromising GABAergic neurotransmission in this region will produce a behavioral phenotype similar to that of blocking excitatory input to this region, or to that of inhibiting neurons in this region, resulting in hyperphagic mouse. We plan to examine these mice behaviorally to assess changes in feeding behavior, weight gain, and metabolism. Together, these integrated, multidisciplinary studies will advance my training as well as elucidate the role of GABAergic transmission in the nucleus accumbens in regulating feeding behavior.